Molecular and Functional Analyses of the Primordial Costimulatory Molecule CD80/86 and Its Receptors CD28 and CD152 (CTLA-4) in a Teleost Fish

Molecular and Functional Analyses of the Primordial Costimulatory Molecule CD80/86 and Its Receptors CD28 and CD152 (CTLA-4) in a Teleost Fish

Blog Article

The moderate activation of T cells in mammals requires the costimulatory molecules, CD80 and CD86, on antigen-presenting cells to interact with their respective T cell receptors, CD28 and CD152 (CTLA-4), to promote costimulatory signals.In contrast, teleost fish (except salmonids) only possess CD80/86 as their sole primordial costimulatory molecule.However, the mechanism, which underlies the interaction between CD80/86 and its receptors CD28 and CD152 still requires elucidation.In this study, we cloned and identified the CD80/86, CD28, and CD152 genes Wall Clocks of the grass carp (Ctenopharyngodon idella).The mRNA expression analysis showed that CD80/86, CD28, and CD152 were constitutively expressed in various tissues.

Further analysis revealed that CD80/86 was highly expressed in IgM+ B cells.Conversely, CD28 and CD152 were highly expressed in CD4+ and CD8+ T cells.Subcellular localization illustrated that CD80/86, CD28, and CD152 are all located on the cell membrane.A yeast two-hybrid assay exhibited that CD80/86 can bind with both CD28 and CD152.In vivo assay showed that the expression of CD80/86 was rapidly upregulated in Aeromonas hydrophila Yard Sign infected fish compared to the control fish.

However, the expression of CD28 and CD152 presented the inverse trend, suggesting that teleost fish may regulate T cell activation through the differential expression of CD28 and CD152.Importantly, we discovered that T cells were more likely to be activated by A.hydrophila after CD152 was blocked by anti-CD152 antibodies.This suggests that the teleost CD152 is an inhibitory receptor of T cell activation, which is similar to the mammalian CD152.Overall, this study begins to define the interaction feature between primordial CD80/86 and its receptors CD28 and CD152 in teleost fish, alongside providing a cross-species understanding of the evolution of the costimulatory signals throughout vertebrates.